Is GATA2 p.Pro125= (c.375A>C) pathogenic?

GATA2 p.Pro125= (c.375A>C) is classified Likely benign in GATA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-15). Rare (popmax 0.292%, mid); Associated with Inborn genetic diseases.

What condition is associated with GATA2 p.Pro125= (c.375A>C)?

GATA2 p.Pro125= (c.375A>C) is associated with Inborn genetic diseases, deafness-lymphedema-leukemia syndrome, monocytopenia with susceptibility to infections (ClinVar).

How common is GATA2 p.Pro125= (c.375A>C) in the general population?

GATA2 p.Pro125= (c.375A>C) is rare (popmax 0.292%, mid) (gnomAD).

GATA2 p.Pro125=

c.375A>C · rs763281230 · VCV412750

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.292%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -3
Overall
CADD	4.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.292% Middle Eastern · 17/5,822 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.153%

Overall 0.00167% 26/1,560,788 alleles · rare exomes 26/1,408,634 · genomes 0/152,154 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.292%	342
Remaining individualsnot grpmax-eligible	0.00826%	12,109
European (non-Finnish)	0.000347%	288,134

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GATA2
Protein: p.Pro125=
Coding: c.375A>C
MANE Select: NM_032638
dbSNP: rs763281230
Type: single nucleotide variant
Location: chr3:128486223 (GRCh38)
Gene constraint: LOEUF 0.335 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.11 · 2 PDB
Residue 125: the 'disordered' region

Full GATA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: deafness-lymphedema-leukemia syndrome monocytopenia with susceptibility to infections

Similar variants

GATA2 p.Pro125Gln Uncertain significance ★ ⚠ same residue
GATA2 c.1017+572C>T Pathogenic/Likely pathogenic ★★ same condition
GATA2 c.1018-1G>T Pathogenic/Likely pathogenic ★★ same condition
GATA2 c.1018-2A>G Pathogenic/Likely pathogenic ★★ same condition
GATA2 c.1018-2A>T Pathogenic ★★ same condition
GATA2 c.1143+2T>A Pathogenic/Likely pathogenic ★★ same condition
GATA2 p.Ala372Thr Likely pathogenic ★★ same condition
GATA2 p.Arg204Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gata2-p-pro125 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown